Pharmacogenetics of cardiac K+ channels

A number of commonly prescribed drugs belonging to various therapeutic classes (antiarrhythmic, antibiotic, antifungal, antihistamine, antipsychotic, prokinetic drugs...)possess, in common, the adverse property to prolong cardiac repolarization [prolonged QT interval duration on surface electrocardiogram (ECG)], exposing patients to a risk of torsade-de-pointes arrhythmias, syncope, and sudden death. Arrhythmias related to drug-induced QT prolongation do not occur in every patient treated with these drugs but most likely occur in a subset of susceptible patients. These patients have a high risk of recurrence of arrhythmias upon exposure to any of the other drugs that broaden the QT interval. It is currently suspected (though not yet proven) that susceptible individuals carry a silent mutation in one of the genes responsible for the congenital long QT syndrome. Indeed, it appears more and more clear that a large proportion of congenital long QT syndrome gene carriers, have a normal QT interval and a normal phenotype and therefore, remain undiagnosed. Therefore, a much larger than previously thought proportion of the general population may be affected by asymptomatic mutations in cardiac ion channel encoding genes. No routine technology is currently available in identifying these patients preventively. (C) 2000 Elsevier Science B.V. All rights reserved.